Synergistic Antileukemic Effect of Theophylline and 1,3-Bis(2-chloroethyl)-1 -nitrosourea1
نویسندگان
چکیده
A series of experiments evaluated the antileukemic effect of an agent which elevates cellular cyclic adenosine 3':5'-monophosphate levels by inhibiting phosphodiesterase. When ad ministered alone, theophylline had only modest antileukemic effects, but it had synergistic effects when administered with 1,3-bis(2-chloroethyl)-1 -nitrosourea. This synergism produced an improved therapeutic index in a dose-response study and in a comparison between antileukemic effects and effects on white blood cell nadirs. Uptake of 1,3-bis(2-chloroethyl)-1 -ni trosourea and studies of timing of treatment support the hy pothesis that elevation of cyclic adenosine 3':5'-monophosphate levels is the mechanism of the observed synergistic effect.
منابع مشابه
Synergistic antileukemic effect of theophylline and 1,3-bis(2-chloroethyl)-1-nitrosourea.
A series of experiments evaluated the antileukemic effect of an agent which elevates cellular cyclic adenosine 3':5'-monophosphate levels by phosphate levels by inhibiting phosphodiesterase. When administered alone, theophylline had only modest antileukemic effects, but it had synergistic effects when administered with 1,3-bis(2-chloroethyl)-1-nitrosourea. This synergism produced an improved th...
متن کاملSynergistic antileukemic effect of 6-aminonicotinamide and 1,3-bis(2-chloroethyl)-1-nitrosourea on L1210 cells in vitro and in vivo.
A series of nicotinamide analogs were evaluated for their ability to inhibit L1210 cell poly(adenosine diphosphoribose) polymerase, and also for their ability to potentiate the cytocidal effects of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), nitrogen mustard, and gamma-irradiation. In L1210 cells growing in culture and in vivo. In vitro, nicotinamide, 5-methylnicotinamide, 6-aminonicotinamide,...
متن کاملInhibition of the Ligase Step of Excision Repair by 2-Chloroethyl Isocyanate, a Decomposition Product of 1,3-Bis(2-chloroethyl)-1- nitrosourea1
The compound 2-chloroethyl isocyanate, a decomposi tion product of 1,3-bis(2-chloroethyl)-1-nitrosourea, was studied for its effects on excision repair of DNA in normal human fibroblasts exposed to ultraviolet (UV) radiation. For examination of the initial step in repair (UV endonuclease), the frequency of UV-induced strand breaks was analyzed by alkaline elution. Repair polymerase activity was...
متن کاملDMA Damage and Repair in the Bone Marrow of Rats Treated with Four Chloroethylnitrosoureas1
DNA is considered to be an important target for the antitumor and toxic properties of the Chloroethylnitrosoureas. Since the main target for their dose-limiting toxicity and the antileukemic efficacy is believed to be the bone marrow, we have compared the formation and subsequent removal of DNA-DNA interstrand cross-links in the bone marrow of rats which had received a single i.p. injection (10...
متن کاملDifferential inhibition of the rejoining of X-ray-induced DNA strand breaks in normal and transformed human fibroblasts treated with 1,3-bis(2-chloroethyl)-1-nitrosourea in vitro.
The effects of 1,3-bis(2-chloroethyl)-1-nitrosourea on the rejoining of X-ray-induced DNA strand breaks were examined in normal human fibroblasts (WI-38) and a simian virus 40-transformed derivative (VA-13) with the use of alkaline sucrose sedimentation. 1,3-Bis(2-chloroethyl)-1-nitrosourea was capable of partially inhibiting repair of X-ray-produced DNA strand breaks in both cell types when th...
متن کامل